Research Topic

Development of the Hypothalamus

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The hypothalamus is the region of the brain in charge of the maintenance of the internal milieu of the organism (e.g. pH, temperature, osmolarity). It is also essential to orchestrate reproductive, parental, aggressive-defensive, and other social behaviors and for the expression of emotions. To perform these ...

The hypothalamus is the region of the brain in charge of the maintenance of the internal milieu of the organism (e.g. pH, temperature, osmolarity). It is also essential to orchestrate reproductive, parental, aggressive-defensive, and other social behaviors and for the expression of emotions. To perform these tasks, essential to the preservation of the individual and propagation of the species, the hypothalamus controls motivated behaviors like eating and drinking, the sleep-wake cycle and the endocrine and autonomic nervous systems.

Hypothalamic structure is correspondingly complex as it is formed by numerous neuronal nuclei of different sizes embedded in a “reticular” matrix of neurons not aggregated into nuclei. Its many parts are connected with each other and with surrounding brain regions by a particularly intricate axonal network. It has taken dedicated neuroanatomists forty years to outline the basic plan and major connectivity pathways of the adult hypothalamus.

Due to the structural complexity of the hypothalamus, its ontogenesis has been neglected for a long time. As a result, many basic aspects of hypothalamic development are still mysterious. A change in morphological paradigm, from earlier columnar interpretations to neuromeric ones, is taking place. How are the rostro-caudal regions and medio-lateral zones of the hypothalamus specified? How do they acquire their differential functionality and connectivity? How does the lateral hypothalamus develop (a region without recognizable nuclear structure but with enormous anatomical and functional complexity)? Which genes control differentiation, specialization and migration of hypothalamic neurons to designated areas?

Even concepts long taken for granted start to be challenged in view of advances in developmental and comparative neurobiology, and notably also in the molecular characterization of hypothalamic structures: how should we understand the position of the hypothalamus in relation to other brain regions? Should we bundle it together with the thalamus, a functionally, genetically and developmentally very different structure? Does the concept of “diencephalon” with or without the hypothalamus make sense (outside its descriptive value in the adult brain)? Does the preoptic area belong to the hypothalamus? The answer to these questions will help to understand hypothalamic evolution and morphogenesis as well as its adult function and connectivity.

Nowadays we assist to a renewal of interest spurred in part by the growing realization that prenatal and early postnatal influences on the hypothalamus could entail pathological conditions later in life. Intriguing questions for the future include: do early specification phenomena reflect on adult hypothalamic function and possibly on some kinds of behavior? Can early events like specification, migration or formation of nuclei influence adult hypothalamic function?

In summary, we feel it is opportune to review the fundamentals of hypothalamic ontogenesis and evolution, bearing on our knowledge of its function and pathology. Here we propose to summarize present-day knowledge, to take stock of the latest advances and to anticipate future challenges. While the neuroanatomical and histological approaches (i.e. “visible” hypothalamus) will form a core of the proposed issue, we will welcome contributions dealing with metabolic, neuroendocrine and behavioral alterations during the formation and maturation of hypothalamic centers and circuits.


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